U.S. patent number 8,858,988 [Application Number 13/505,978] was granted by the patent office on 2014-10-14 for compositions comprising extracts of boswellia, tea tree, aloe and lavender oil and methods of treating wounds, burns and skin injuries therewith.
This patent grant is currently assigned to CuraPhyte Technologies Inc., Nutriquine N.V.. The grantee listed for this patent is Peter Bollen, Guy Chamberland. Invention is credited to Peter Bollen, Guy Chamberland.
United States Patent |
8,858,988 |
Chamberland , et
al. |
October 14, 2014 |
Compositions comprising extracts of Boswellia, tea tree, aloe and
lavender oil and methods of treating wounds, burns and skin
injuries therewith
Abstract
Compositions for the treatment of sores, wounds, burns and other
traumatized dermal tissues and skin injuries comprising Boswellia
gum, gel, resin or extract, Tea Tree oil (Melaleuca oil), an Aloe
gel, resin, latex or extract and Lavender oil. The composition may
be incorporated into a medical device such as a wound dressing or
bandage, or formulated into a topical preparation such as an
ointment, lotion or cream.
Inventors: |
Chamberland; Guy (Boucherville,
CA), Bollen; Peter (B-Drongen, BE) |
Applicant: |
Name |
City |
State |
Country |
Type |
Chamberland; Guy
Bollen; Peter |
Boucherville
B-Drongen |
N/A
N/A |
CA
BE |
|
|
Assignee: |
CuraPhyte Technologies Inc.
(Boucherville, CA)
Nutriquine N.V. (Drongen, BE)
|
Family
ID: |
43969515 |
Appl.
No.: |
13/505,978 |
Filed: |
November 2, 2010 |
PCT
Filed: |
November 02, 2010 |
PCT No.: |
PCT/CA2010/001740 |
371(c)(1),(2),(4) Date: |
July 26, 2012 |
PCT
Pub. No.: |
WO2011/054090 |
PCT
Pub. Date: |
May 12, 2011 |
Prior Publication Data
|
|
|
|
Document
Identifier |
Publication Date |
|
US 20120308637 A1 |
Dec 6, 2012 |
|
Foreign Application Priority Data
Current U.S.
Class: |
424/445; 424/489;
424/572; 424/195.17; 424/529; 424/450; 424/642; 424/535; 424/744;
424/400; 424/447 |
Current CPC
Class: |
A61P
29/00 (20180101); A61P 17/00 (20180101); A61L
15/34 (20130101); A61K 36/324 (20130101); A61P
31/00 (20180101); A61P 17/02 (20180101); A61L
15/40 (20130101); A61L 15/44 (20130101); A61K
36/53 (20130101); A61K 36/61 (20130101); A61K
36/886 (20130101); A61K 36/324 (20130101); A61K
2300/00 (20130101); A61K 36/53 (20130101); A61K
2300/00 (20130101); A61K 36/61 (20130101); A61K
2300/00 (20130101); A61K 36/886 (20130101); A61K
2300/00 (20130101); A61L 2300/30 (20130101); A61L
2300/62 (20130101) |
Current International
Class: |
A61L
15/00 (20060101); A61K 35/20 (20060101); A61K
35/14 (20060101); A61K 9/14 (20060101); A01N
59/16 (20060101); A61L 15/16 (20060101); A61K
9/00 (20060101); A01N 65/00 (20090101); A61K
35/12 (20060101); A61K 9/127 (20060101) |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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|
|
|
|
|
|
2557968 |
|
Sep 2005 |
|
CA |
|
2583562 |
|
Apr 2006 |
|
CA |
|
WO 2006040119 |
|
Jul 2006 |
|
WO |
|
WO 2008134712 |
|
Nov 2008 |
|
WO |
|
Other References
Tea tree oil (http://en.wikipedia.org/wiki/Tea.sub.--tree.sub.--oil
(downloaded on Jul. 24, 2013)). cited by examiner .
Lavandula angustifolia
(http://web.archive.org/web/20090801042327/http://en.wikipedia.org/wiki/L-
avandula.sub.--angustifolia (archived on Aug. 1, 2009)). cited by
examiner .
Gauze
(http://web.archive.org/web/20090224214950/http://en.wikipedia.org/w-
iki/Gauze (archived on Feb. 24, 2009)). cited by examiner .
Abu Bakr Mohammad Bin Zakariyya Al-Razi, Formulation ID: AA12/527,
Traditional Knowledge Digital Library Database (TKDL) (1962).
English Translation from Kitaab-al-Haawi-fil-Tibb, vol. XII
(9.sup.th Century AD), Dayerah-al-Ma'aarif Usmania, Hyderabad,
India, (First Edition) p. 236. cited by applicant .
Farnsworth et al., "Medicinal Plants in Therapy," Bulletin of the
World Health Organization 63:965-981 (1985). cited by applicant
.
Mohammad Akmal Khan, Formulation ID: AH5/253F, Traditional
Knowledge Digital Library Database (TKDL) (1909). English
Translation from Qaraabaadeen Azam wa Akmal (20.sup.th Century AD),
Matba Siddiqi/Matba Mustafai, Delhi, India, p. 362. cited by
applicant .
Kerr, "The Use of Essential Oils in Healing Wounds, " International
Journal of Aromatherapy 12:202-206 (2002). cited by applicant .
International Search Report and Written Opinion for International
Application No. PCT/CA2010/001740, dated Feb. 11, 2011 (12 pages).
cited by applicant .
International Preliminary Report on Patentability for International
Application No. PCT/CA2010/001740 dated May 18, 2012 (8 Pages).
cited by applicant.
|
Primary Examiner: Hartley; Michael G
Assistant Examiner: Kim; Sun Y
Attorney, Agent or Firm: Clark & Elbing LLP
Claims
What is claimed is:
1. A composition for treating sores, wounds, burns or other
traumatized dermal tissues and skin injuries, formulated into a
topical ointment, lotion or cream comprising about 2% by weight oil
from the leaves of Melaleuca alternifolia (Tea Tree oil); about
2.8% by weight gum from the resin of Boswellia serrata (boswellia);
about 1% by weight to about 10% by weight gel from the leaves of
Aloe vera (Aloe); and about 0.4% by weight oil from the flower of
Lavandula officinalis (Lavender).
2. The composition of claim 1, further comprising Lanolin, Zinc
oxide, Cod Liver oil, Paraffinum Liquidum, white petroleum jelly,
Propyl hydroxybenzoate, Methyl hydroxybenzoate and water.
3. The composition of claim 2, further comprising an alginate, a
hydrocolloid, or combinations thereof.
4. The composition according to claim 1, wherein the composition
comprises about 50% to 79% by weight boswellic acids.
5. The composition according to claim 1, wherein the Tea Tree oil
contains at least 10% by weight terpinene-4-ol.
6. The composition according to claim 1, further comprising one or
more component or extract containing growth factors; an antibiotic;
an analgesic; zinc oxide; vitamin A; vitamin E; an extract of
Harpagophytum procumens (Devil's claw) root, Salix Alba (White
Willow) plant or bark, Tanacetum Parthenium (Feverfew) herb or
flower, Equisetum arvense (Horsetail), Spireae ulmaria(Dropwort),
Betula alba (Birch), Urtica dioica (Stinging Nettle), Curcuma,
longa (Tumeric), marine algae or Gotu kola (Centella asiatica
Linn.); total triterpenic fraction of Centella asiatica (TTECA); or
combinations thereof.
7. The composition according to claim 6, wherein the component or
extract containing growth factors comprises colostrum, whey, blood,
tissue, or combinations thereof.
8. The composition according to claim 1, further comprising a
component to absorb wound exudates, slowly release the active
agents, or both.
9. The composition according to claim 8, wherein the one or more
components to absorb wound exudates, slowly release the active
agents or both is selected from the group consisting of alginate,
chitosan, hydrocolloid, chitin, polyoligosaccharide, liposome, a
slow-releasing polymer or agent, and combinations thereof.
10. The composition of claim 9, wherein the hydrocolloid comprises
a natural, chemically modified, or synthetic hydrocolloid, or a
combination thereof.
11. The composition of claim 9, wherein the alginate comprises
calcium alginate.
12. The composition of claim 1, further comprising one or more
non-plant component selected from the group consisting of Lanolin,
petroleum jelly, Paraffin oil, Zinc oxide, cod liver oil, vegetable
oil, and paraffinium liquid.
13. The composition of claim 1, further comprising a
preservative.
14. The composition of claim 13, wherein the preservative is a
hydroxybenzoate.
15. The composition of claim 1, further comprising a scent agent to
camouflage the odour of the composition.
16. The composition of claim 15, wherein the scent agent comprises
an essential oil of a plant, flower, or combination thereof.
17. The composition of claim 1, added to, coated on or embedded
into a wound dressing or bandage.
18. The composition of claim 17, wherein the wound dressing is a
fibrous wound dressing or a dressing for applying directly to
wounds for occlusion or semi-occlusion.
19. The composition of claim 1, formulated within or on the surface
of a medical device.
20. The composition of claim 19, wherein the medical device is a
dressing, a bandage, or other semi-occlusive or occlusive material
used in wound care.
21. A medical device comprising the composition as defined in claim
1, coated thereon or embedded within said medical device.
22. The medical device of claim 21, wherein the composition is
contained at least partially within particles or
microparticles.
23. The medical device of claim 22, wherein the particles or
microparticles are liposomes.
24. The medical device of claim 22, wherein the particles or
microparticles comprising the composition are used to deliver or
release active ingredients to the wound while maintaining
semi-occlusion or complete occlusion.
25. The medical device of claim 21, wherein the medical device is a
dressing, a bandage, or other semi-occlusive or occlusive material
used in wound care.
26. A method of treating sores, wounds, burns or other traumatized
dermal tissues and skin injuries, comprising administering a
composition as defined in claim 1 to a subject in need thereof.
27. The method of claim 26, wherein the composition is applied
daily until there is at least partial healing or amelioration of
the sore, wound, burn or other traumatized dermal tissue or skin
injury.
28. The method of claim 26, wherein the method comprises treating
acute wounds selected from the group consisting of heat burns, sun
burns, traumatic injuries, surgical wounds, punctures, cracked
heals, bites, insect bites and infected wounds.
29. The method of claim 26, wherein the method comprises treating
chronic wounds selected from the group consisting of venous leg
ulcers, pressure sores or ulcers, ischemic ulcers and diabetic
ulcers.
30. The method of claim 26, wherein the subject is a mammal.
31. The method of claim 30, wherein the mammal is a human.
Description
FIELD OF INVENTION
The present invention relates to generally to compositions for the
treatment of sores, wounds, burns and other traumatized dermal
tissues and skin injuries. More specifically, the present invention
relates to compositions comprising plant extracts, medical devices
incorporating these compositions, and methods of treating sores,
wounds, burns and other traumatize dermal tissues and skin injuries
therewith.
BACKGROUND OF THE INVENTION
Wound healing is a complex process that some researchers divide
into 3 phases of evolution: inflammatory phase, proliferation, and
remodeling (1). The inflammatory phase is the first response to an
injury and involves multiple responses that include both a cellular
and chemokine/cytokine response. The response includes blood
coagulation, infiltration of leukocytes, etc. This first phase of
response leads to the initiation of the proliferative response for
wound healing. In fact, these two first phases overlap and multiple
factors influence the phases. An important part of the
proliferative phase is the formation of epithelium to cover the
wound surface. The epithelialization reaction occurs somewhat in
parallel to the growth of granulation tissue that is required to
fill the wounds "empty" space. According to Li et al (1), the
granulation tissue formation is the result of the proliferation of
fibroblasts deposition of collagens and other materials along with
an angiogenic process for the formation of new blood vessels.
Finally, the third phase is a remodeling phase that involves
restoring the structural integrity and functional aspects of the
site (1). Every phase of the wound healing process can be
influenced by factors such as infection, that will either increase
the tissue damage and/or prolong the healing time, as well as dead
skin, bleeding, mechanical damage (compression of tissue and
friction), dryness, etc.
There are several types of wounds, but they can generally be
summarized as either acute or chronic. Acute wounds normally heal
without delay and complications, and include burns, traumatic
injuries and surgical wounds. Chronic wounds are those that involve
a disruption of the wound healing process that results in
consequences such as a prolonged time to heal, recurrence or simply
non-healing (1). Chronic wounds include venous leg ulcers, pressure
sores/ulcers, ischemic ulcers, diabetic ulcers, etc.
Management of Wounds
Each wound is unique and multiple factors influence the methods
used to help heal. These factors include the location and size of
the injury, the type of injury (e.g. incision, burn), depth of the
wound and other tissues involved in injury (i.e., nerves), foreign
material in the wound as well as infection, complications during
healing that prolong healing time, and genetic or
pathophysiological factors influencing the different parameters of
healing.
The type of wound closure plays a major role in the healing
process. Closure by primary intent is defined as wound closure
immediately following the injury and prior to the development of
the granulation tissue. Healing by primary intent ultimately leads
to the fastest healing and optimal cosmetic result. Closure by
secondary intent is defined as the process where wounds heal on
their own without surgical closure. Closure by tertiary intent is
defined as a first treatment phase where the wound is cleaned and
dressings are applied and a second phase several days later for
wound closure.
Methods of treating a wound may include one or more steps as
necessary to facilitate healing, prevent infection and
complications, limit scarring and hyperpigmentation, etc. Treatment
may include cleaning the wound to remove foreign material; removing
dead skin; closing (in the case of large wounds) with stitching
type materials (e.g., sutures); dressing the wound; relieving pain;
and treating signs of infection.
In the case of chronic wounds such as pressure or diabetic ulcers,
additional treatments may be required. These are generally aimed at
trying to improve blood flow to the site of injury to promote
healing of the wound/ulcer. Methods involving the use of absorbent
dressings and compression bandages typically help improve blood
flow.
In addition to the above treatment methods, various substances,
both naturally occurring and synthetic, may be employed to promote
healing of skin tissues. These are often applied directly to the
area of the wound or sore in the form of a lotion or ointment, or
incorporated into a bandage, dressing or other device to promote
healing while the device is in use.
For example, U.S. Pat. No. 5,266,318 describes a composition for
treatment of irradiated skin, open sores, wounds and abrasions.
This composition is comprised of an aloe vera gel extract,
allantoin and lavender essential oil.
Another composition for the treatment of wounds and related
conditions is described in U.S. Pat. No. 5,879,717, which is
comprised of a sugar, iodine and a glycol or water vehicle, and is
specifically designed for use in veterinary medicine.
A further composition, which is described in U.S. Pat. No.
5,980,875, is prepared by mixing honey with oil, a gelling agent,
an emulsifier and other components, and is used for the treatment
of Herpes, cold sores, burns, skin allergies and other wounds.
Additionally, U.S. Pat. No. 6,099,866 describes a combination of
beeswax with oil and optionally water to produce a composition for
treatment of various burns and abrasions.
As can be seen, numerous compositions and combinations are known to
assist in the treatment and healing of wounds and skin injury.
Nevertheless, research continues in this area in order to develop
new compositions with improved effectiveness and/or reduced
side-effects.
SUMMARY OF THE INVENTION
An object of the invention is therefore to provide compositions and
methods for treating sores, wounds, burns and other traumatized
dermal tissues and skin injuries.
The invention accordingly relates to compositions comprising plant
extracts useful for treating sores, wounds, burns and other
traumatized dermal tissues and skin injuries, as well as medical
devices comprising such compositions.
In certain non-limiting embodiments the medical device may be a
dressing or a bandage, or may comprise a slow-release polymer,
alginate, oligosaccharides (poly-), chitin, or hydrocolloids.
The invention also relates to methods for treating sores, wounds,
burns and other traumatized dermal tissues and skin injuries in a
subject, comprising administering a composition or medical device
as described herein. Preferably, treating a subject with a
composition or medical device as defined herein results in at least
partial healing or amelioration of the sore, wound, burn or other
traumatized dermal tissue or skin injury.
In an embodiment of the invention, the composition comprises
Boswellia gum, gel, resin or extract, Tea Tree oil (Melaleuca oil),
Aloe gel, resin, latex or extract and Lavender oil.
Without wishing to be limiting, the Boswellia gum, gel, resin or
extract may be derived from the leaves, plant or roots of Boswellia
serrata or other species of Boswellia, such as Boswellia sacra or
Boswellia carterii. In a preferred embodiment, the composition
comprises about 10% to 99% boswellic acids (e.g. as measured by
UV-VIS spectrometry analysis, HPLC Diode array or the like).
The Tea Tree oil (Melaleuca oil), which is also known as Australian
tea tree oil (Melaleuca alternifolia) may, in a further
non-limiting embodiment, be derived from Melaleuca leaves, root or
plant and may contain more than >10% terpinene-4-ol (e.g. as
measured by GC FID or ECD).
The Aloe gel, resin, latex or extract (aqueous or alcoholic
extract) may, in a further non-limiting embodiment, be derived from
the leaves, root or plant of Aloe including, but not limited to
Aloe vera, Aloe africana, Aloe arborescens Miller, Aloe
barbadensis, Aloe barbadesis, and Aloe capensis.
The Lavender oil may, in a further non-limiting embodiment, be
derived from the leaves, root, flower or plant of Lavandula
officinalis or another species of Lavender such as common lavender,
English lavender, garden lavender, Lavandula angustifolia,
Lavandula burnamii, Lavandula dentate, Lavandula dhofarensis,
Lavandula latifolia, Lavandula officinalis, or Lavandula
stoechas.
In further non-limiting embodiments, the compositions described
herein may additionally comprise one or more components or extracts
containing growth factors (including but not limited to growth
factors from colostrum, whey, blood or tissue), antibiotics,
analgesics, zinc oxide, vitamin A, vitamin E, extracts of
Harpagophytum procumens (Devil's claw) root, Salix Alba (White
Willow) plant and/or bark, Tanacetum Parthenium (Feverfew) herb
and/or flower, Equisetum arvense (Horsetail), Spireae ulmaria
(Dropwort), Betula alba (Birch), Urtica dioica (Stinging Nettle),
Curcumin extract, longa (Tumeric), marine algae, or Gotu kola
(Centella asiatica Linn.), total triterpenic fraction of Centella
asiatica (TTECA), or combinations thereof.
The present invention also provides a composition as described
above, wherein the composition further comprises one or more
components to absorb wound exudates and/or slowly release the
active herbal ingredients. These components may include, but are
not limited to alginate, hydrocolloid, chitin,
polyoligosaccharides, liposome, slow-releasing polymers or agent,
or combinations thereof.
The composition as described herein may, in further non-limiting
embodiments, be formulated within or on the surface of a medical
device. The medical device may be, in certain exemplary embodiments
which are also considered to be non-limiting, a dressing, bandage,
or other semi-occlusive or occlusive material commonly used in
wound care. As an example, the composition may be coated onto the
medical device, or embedded or contained within particles or
microparticles such as liposomes. For instance, the particles or
microparticles comprising the composition as described herein may
be used to deliver or release the active herbal ingredients to the
wound while maintaining semi-occlusion or complete occlusion.
As mentioned above, the present invention also relates to a method
of treating sores, wounds, burns and other traumatized dermal
tissues and skin injuries. In certain non-limiting embodiments, the
method involves treating acute wounds, such as but not limited to
heat and sun burns, traumatic injuries, surgical wounds, punctures,
cracked heals, bites, insect bites and infected wounds. In other
non-limiting embodiments, the method involves treating chronic
wounds, such as but not limited to venous leg ulcers, pressure
sores or ulcers, ischemic ulcers and diabetic ulcers. When treating
a surgical wound, in a non-limiting embodiment of the described
method, the a composition or medical device as described herein may
be administered to an incision which has been sutured, or to a
wound which has been closed with surgical thread or the like, in
order to promote healing of the incision or wound.
According to the methods described herein, the subject may be a
mammalian subject, and in further non-limiting embodiments the
subject may be a human.
This summary of the invention does not necessarily describe all
features of the invention. In addition, those skilled in the art
will recognize, or be able to ascertain using no more than routine
experimentation, numerous equivalents to the specific procedures
described herein. Such equivalents are considered to be within the
scope of this invention and are covered by the following
claims.
BRIEF DESCRIPTION OF THE FIGURES
Further details of the invention will become apparent from the
following description, taken in combination with the appended
figure wherein:
FIG. 1 illustrates a plot of the time course of wound healing in
mouse cutaneous injury model. Test substance was administered
topically (TOP) once or twice or three times daily for 10
consecutive days. The wound closure (%) was determined on days 3,
5, 7, 9 and 11, and then the wound half-closure time (CT.sub.50)
was obtained. One-way ANOVA followed by Dunnett's test was applied
for comparison between the treated and vehicle groups. *P<0.05,
vs. vehicle.
DETAILED DESCRIPTION
Described herein are plant extracts which are useful for treating
sores, wounds, burns and other traumatized dermal tissues and skin
injuries therewith. The described extracts can be provided in
compositions together with an acceptable carrier, and/or together
with one or more separate active agents. They can also be
incorporated into a medical device as described herein, or used in
a method of treating sores, wounds, burns and other traumatized
dermal tissues and skin injuries.
The following description is of a preferred embodiment.
According to the present invention, there is provided a composition
comprising Boswellia gum, gel, resin or extract, Tea Tree oil
(Melaleuca oil), an Aloe gel, resin, latex or extract and Lavender
oil. Other components may also be included as described herein and
throughout.
In an embodiment, the Boswellia gum, gel, resin or extract is
derived from the leaves, plant or roots of Boswellia serrata, or
other species of Boswellia such as Boswellia sacra, Boswellia
carterii, and contains between about 10% and 99% boswellic acids,
for example but not limited to about 10%, 20%, 30%, 40%, 50%, 60%,
70%, 80%, 90%, 99% or any value therein between. The amount of
boswellic acids may also be defined by a range of any two of the
values listed above or any value therein between, and can be
measured, for instance, by UV-VIS spectrometry analysis, HPLC Diode
array or other non-limiting method. More preferably the Boswellia
gum, gel, resin or extract contains between about 50% to 79%
boswellic acids.
The Tea Tree oil (Melaleuca oil), also known as Australian tea tree
oil, may be derived from the leaves, root or plant of Melaleuca
alternifolia and, in a non-limiting embodiment contains more than
10% terpinene-4-ol as measured by GC FID, ECD or other non-limiting
method comparable thereto (GC: gas chromatography; FID: Flame
Ionization Detector; ECD: Electron Capture Detector).
The Aloe gel, resin, latex or extract (aqueous or alcoholic
extract) may be derived from the leaves, root or plant of Aloe
(including but not limited to Aloe vera, Aloe africana, Aloe
arborescens Miller, Aloe barbadensis, Aloe barbadesis, or Aloe
capensis).
The Lavender oil may be derived from the leaves, flower, plant or
root of Lavandula officinalis, or another species of Lavender such
as common lavender, English lavender, garden lavender, Lavandula
angustifolia, Lavandula burnamii, Lavandula dentate, Lavandula
dhofarensis, Lavandula latifolia, Lavandula officinalis, or
Lavandula stoechas.
The present invention also contemplates compositions comprising
components in addition to and outside the ranges provided
above.
The composition described herein may also comprise additional
components or extracts containing growth factors (such as from
colostrum, whey, blood or tissue), antibiotics, analgesics, zinc
oxide, vitamin A, vitamin E, or extracts of Harpagophytum procumens
(Devil's claw) root, Salix Alba (White Willow) plant and/or bark,
Tanacetum Parthenium (Feverfew) herb and/or flower, Equisetum
arvense (Horsetail), Spireae ulmaria (Dropwort), Betula alba
(Birch), Urtica dioica (Stinging Nettle), Curcumin extract, longa
(Tumeric), marine algae, Gotu kola (Centella asiatica Linn.), total
triterpenic fraction of Centella asiatica (TTECA) or a combination
thereof.
In addition, the composition described herein may comprise one or
more additional non-plant component, for example, but not limited
to Lanolin, petroleum jelly (e.g. Vaseline.TM.), Paraffin oil, Zinc
oxide, cod liver oil, vegetable oil, paraffinium liquid, and one or
more preservative, for example, but not limited to
hydroxybenzoates, or scent agents to camouflage the odor of the
formulation, for example, but not limited to essential oils of
plants/flowers, or any combination thereof.
Without wishing to be limiting in any manner, the composition may
be formulated into a suitable topical dosage form, for example, but
not limited to an ointment, lotion or cream that may be applied
topically to a wound or site of skin injury as such. More
preferably, the composition is formulated into ointments for
applying to wounds. For example, but not wishing to be limiting in
any manner, an ointment comprising 2% oil from the leaves of
Melaleuca alternifolia (Tea Tree oil); 2.8% gum from the resin of
Boswellia serrata (boswellia); 1% of a 10% gel from the leaves of
Aloe vera (Aloe); 0.4% oil from the flower of Lavandula officinalis
(Lavender), Lanolin, Zinc oxide, Cod Liver oil, Paraffinum
Liquidum, Vaseline.TM. White, Propyl hydroxybenzoate, Methyl
hydroxybenzoate, and water can be prepared using standard
procedures known in the art. The composition may also comprise
additional components including, but not limited to, alginate,
hydrocolloid and or other components.
In a further non-limiting embodiment of the invention, the plant
ointment is prepared by warming the lanolin (9 kg), Vaseline.TM. (9
kg) and paraffin (10 kg) together to +/-55.degree. C. so the mix is
a fluid liquid. Ten kg of a 22% concentrate of Boswellia serrata
gum or resin, Tea Tree oil (Melaleuca oil), Aloe vera gel, and
Lavender oil (Lavandula officinalis) is prepared and warmed to
30-35.degree. C. and a clear liquid is obtained. After that, the
first liquid is added in a tub (pit) with a mixer, thereafter the
second liquid is added (warmed Lurax concentrate). In a preferred
embodiment, the mixer is a high power mixer with sufficient power
to mix the reagents, although it does not have to turn quickly,
similar to a dough-kneader. Once well mixed (e.g. after
approximately 10-15 minutes), approximately 7.2 kg of zinc oxide
may be added. After 5 minutes of further mixing, the warm ointment
can be filled into a container.
In another non-limiting embodiment, there is provided a composition
to obtain a wound dressing or wound foam comprising 2% oil from the
leaves of Melaleuca alternifolia (Tea Tree oil); 2.8% gum from the
resin of Boswellia serrata (boswellia); 1% gel from the leaves of
Aloe vera (Aloe); 0.4% oil from the flower of Lavandula officinalis
(Lavender), Lanolin, Zinc oxide, Cod Liver oil, Paraffinum
Liquidum, Vaseline.TM. White, Propyl hydroxybenzoate, Methyl
hydroxybenzoate, Water and an absorptive agent such as, but not
limited to, calcium alginate, chitosan or hydrocolloid (natural,
chemically modified, and/or synthetic hydrocolloids).
In a further embodiment, there is provided a composition comprising
2% oil from the leaves of Melaleuca alternifolia (Tea Tree oil);
2.8% gum from the resin of Boswellia serrata (boswellia); 1% gel
from the leaves of Aloe vera (Aloe); 0.4% oil from the flower of
Lavandula officinalis (Lavender), Lanolin, Zinc oxide, Cod Liver
oil, Paraffinum Liquidum, Vaseline.TM. White, Propyl
hydroxybenzoate, Methyl hydroxybenzoate, Water and an absorptive
agent such as, but not limited to, calcium alginate, chitosan or
hydrocolloid (natural, chemically modified, and/or synthetic
hydrocolloids) and this composition is added to, coated or embedded
into a fibrous wound dressing, bandage or other type of dressing
for applying directly to wounds.
It is intended that the present invention includes additional
embodiments of the specific preparations and preparative methods
described above. Variations according to the knowledge of one
skilled in the art such as by scale, i.e. by scaling-up or
scaling-down the described parameters. Further, the specified time
and temperature ranges specified above should be considered to be
exemplary for the purpose of enabling one to practice the
invention, and therefore non-limiting.
The present invention also contemplates a method of treating
wounds, sun burns, heat burns, skin injuries, insect bites,
surgical incision wounds, traumatic wounds, cracked heals, skin
ulcers, diabetic ulcers, pressure ulcers or other skin injury
conditions and the like by administering a composition, ointment or
dressing composition as described herein to a subject in need
thereof. In a preferred embodiment, which is not meant to be
limiting in any manner, it is generally preferred that the
composition, ointment or dressing composition, as described herein,
be applied daily until the wound is closed/healed.
Definitions:
A "dressing" is an adjunct used for application to a wound to
promote healing and/or prevent further harm. It is designed to be
in direct contact with the wound. The dressing may be a piece of
material, such as cloth or gauze, a film, a gel, a foam, chitin, a
hydrocolloid, an alginate, a hydrogel, or a polysaccharide paste,
granules or beads. Dressings can be impregnated with any desired
antiseptic chemicals, an agent designed to speed healing, or other
active agent as is known in the art or described herein.
A "bandage" is a piece of material used either to support a medical
device such as a dressing, or on its own to provide support to the
body. Bandages may take a wide range of forms, from generic cloth
strips, to specialized shaped bandages designed for a specific limb
or part of the body. In certain embodiments, a "bandage" may also
refer to a supporting material and a dressing which is used
directly on a wound.
"Chitin" is a polymer comprising units of N-acetyl-D-glucos-2-amine
covalently linked with .beta.-1,4 linkages. Medical devices as
described herein may comprise chitin in order to take advantage of
its properties as a flexible and strong material, as well as its
biodegradability. In certain embodiments, chitin may be
incorporated into a dressing, or other non-limiting medical
device.
A "hydrocolloid" is defined as a colloid system wherein the colloid
particles are dispersed in water. A hydrocolloid has colloid
particles spread throughout water, and depending on the quantity of
water available that can take place in different states, e.g., gel
or sol (liquid). Hydrocolloids can be either irreversible
(single-state) or reversible. Hydrocolloids can be derived from
natural or synthetic sources. Non-limiting examples of natural
hydrocolloids include agar-agar, carrageenan, gelatin, and pectin.
In hydrocolloid-based medical dressings, the hydrocolloid may
interact with tissue fluid to form a nonadhesive gel.
"Alginate" is a salt of alginic acid, typically extracted from
marine kelp. Certain alginates, including but not limited to
calcium, sodium, and ammonium alginates, can be used in foam,
cloth, or gauze for absorbent surgical dressings.
The present invention will be further illustrated in the following
examples.
EXAMPLES
Animal model: Groups of 8 ICR male mice weighing 22.+-.2 g were
used. Under ether anesthesia, the shoulder and back region of each
animal was shaved. A sharp punch (ID 12 mm) was used to remove the
skin including panniculus carnosus and adherent tissues. The wound
area, traced onto clear plastic sheets on days 3, 5, 7, 9 and 11,
were quantitated by use of an Image Analyzer (Life Science
Resources VISTA, Version 30). Test compound and vehicle (20 .mu.l,
1.5% carboxymethylcellulose in PBS) were applied topically
immediately following injury and in single, two or three
applications daily thereafter for a total of 10 consecutive days.
The wound half-closure time (CT.sub.50) was determined and unpaired
Student's t test was applied for comparison between treated and
vehicle group at each measurement time point. Differences are
considered statistical significance at P<0.05. CGS-21680
((2-p-carboxyethyl)phenylamino-5'-N-carboxamidoadenosine) was used
as a positive comparator.
Test substance C-T-1001 (Ointment A: herbal active ingredients tea
tree oil, boswellia resin, aloe vera gel and lavender oil) was
evaluated for possible wound healing activity. The test substance
was applied topically to the wound area once, twice, or three times
daily for 10 consecutive days. Percent closure of the wound (%) was
determined on days 3, 5, 7, 9 and 11 in order to generate the half
closure time (CT50). One-way ANOVA followed by Dunnett's test was
used to determine significant difference between the treated groups
and vehicle control. It was concluded that topical administration
of C-T-1001 at 20 mg/mouse for 10 consecutive days promoted
significant increase in wound closure during the observation period
from day 7 to day 11, in proportion to frequency of daily
treatment; C-T-1001 at 20 mg/mouse 2 and 3 times daily, but not
once a day treatment, was associated with a significant decrease in
CT50 value in the mouse model of cutaneous injury. The results are
summarized in Table 1 and FIG. 1.
TABLE-US-00001 TABLE 1 Summary of animal test data The Closure of
Wound (%) CT.sub.50 Treatment Route Dose Day 3 Day 5 Day 7 Day 9
Day 11 (Days) Vehicle TOP 20 .mu.l/mouse .times. 10 X 26.7 43.0
52.8 65.9 73.2 6.9 (1.5% CMC/PBS pH7.4) SEM 3.4 3.0 2.2 1.9 1.9 0.3
C-T-1001 TOP 20 mg/mouse qd .times. 10 X 9.5 25.6 54.2 77.4* 88.3*
6.8 SEM 2.8 2.2 3.2 1.2 1.0 0.1 C-T-1001 TOP 20 mg/mouse bid
.times. 10 X 13.7 37.2 63.6* 84.6* 91.0* 6.2* SEM 2.5 3.3 1.6 1.2
0.7 0.1 C-T-1001 TOP 20 mg/mouse tid .times. 10 X 14.2 36.5 67.9*
86.0* 94.9* 6.0* SEM 2.9 2.5 3.1 1.7 1.3 0.1 CGS-21680 TOP 10
.mu.g/mouse .times. 10 X 42.4* 56.3* 66.8* 74.3* 81.7* 5.5* SEM 1.7
1.5 2.3 1.3 0.6 0.1 The closure of the wound (%) and wound
half-closure time (CT.sub.50) were determined. One-way ANOVA
followed by Dunnett's test was used for comparison between the
treated and vehicle groups. *P < 0.05, vs. vehicle.
Human Clinical Trial:
Summary--In a 30-day clinical trial, the benefits of several
formulations of the herbal active ingredients tea tree oil,
boswellia resin, aloe vera gel and lavender oil, on wound healing
were assessed in six uniform wounds created by using a fractional
CO.sub.2 laser in over 30 healthy human volunteers. The
formulations were compared and tested on each of the over 30
volunteers. The formulations were applied to wounds daily, and
occluded with a bandage dressing, for a period of 30 days. After
one week of treatment, hydrophilic ointment formulations performed
significantly better than Polysporin.TM. and Petrolatum for
erythema, epithelialization, and maceration. Throughout the 30-day
study (days 14, 21) the hydrophilic ointment formulations performed
better for erythema. In addition, the hydrophilic ointment
formulations performed better than Petrolatum and Polysporin.TM.
for scarring and hyperpigmentation. The study also demonstrated
that a higher degree of occlusion would ameliorate the healing of
the wound.
Clinical Trial Details--The 30-day controlled trial was conducted
to assess the effects for five topically applied agents on wound
healing in six uniform wounds created by using a CO.sub.2 laser. At
Baseline, one negative control site and five test sites were marked
on the ventral forearms (three sites per arm) and the Investigator
created five uniform wounds, approximately 100 microns deep and 1
centimeter in diameter, using a fractional CO.sub.2 laser set at a
regular mode at the five test sites; the negative control site was
not exposed to the laser. A total of 31 human volunteers completed
the study. Five formulations were evaluated in this study. Ointment
A: multi-herbal ointment that was more fluid than thick in
consistency. Ointment B: multi-herbal ointment that was thick in
consistency. Ointments A and B had the exact same quantities of
active ingredients and non-medicinal ingredients and the only
difference was the blending method that made the ointment thicker.
Ointment A and ointment B contained the herbal active ingredients
tea tree oil, boswellia resin, aloe vera gel and lavender oil.
Cream C: multi-herbal topical formulation that also contained the
exact same quantity of active ingredients as ointments A and B but
it did not contain the same non-medicinal ingredients. Cream C is a
hydrophilic formulation. Formulation D: a commercial preparation of
Petrolatum. Formulation E: Polysporin.TM..
After Baseline evaluations, the human volunteers applied the
formulations twice daily to the assigned test (the control site was
left untreated) site and subsequently (each time) an adhesive
bandage was applied over the wound site.
Evaluations were conducted, blinded by the investigator, at Day 1,
Day 4, Day 7, Day 14, Day 21, and Day 30. At baseline and Days 1,
4, 7, 14 and 21, evaluations consisted of: grading for erythema,
edema, epithelialization, maceration and scabbing. On Day 30, the
wounds were visually graded for Scar Formation (Scar Formation
(0=healthy, normal skin and 10=keloid, hypertrophic, or other scar
present) and Post-Inflammatory Hyperpigmentation (Post-Inflammatory
Hyperpigmentation (0=none and 10=severe).
Overall, after one week of treatment, ointments A and B performed
better than formulations D and E for erythema, epithelialization,
and maceration. At Days 14 and 21, the ointments A and B continued
to perform better for erythema. Formulations D and E performed
better than ointments A and B for scabbing and hydration, starting
after two weeks of treatment. This was due to the highly occlusive
nature of test formulations D and E (Petrolatum and Polysporin.TM.,
respectively).
Mean values for clinical grading at each time point (Days 1, 4, 7,
14, 21 and 30) were statistically compared to mean Baseline values
using analysis of variance (ANOVA) with pair-wise comparisons
(Fisher's LSD) and paired t-tests at the p.ltoreq.0.05 significance
level. Mean percent change from Baseline and incidence of positive
responders were calculated for all attributes.
The results are presented in Table 2 below. It should be noted that
the Cream C was discontinued from the study due to poor healing
during the first week of treatment. The results provided are only
for Ointments A and B and Formulations D and E.
TABLE-US-00002 TABLE 2 Mean Values For Clinical Grading Baseline
Day 1 Day 4 Day 7 Day 14 Day 21 Treatment (n = 31) (n = 31) (n =
31) (n = 31) (n = 31) (n = 30) Erythema A 1.87 2.16 2.94
.largecircle. 3.48 .largecircle. 3.84 .largecir- cle. 3.77
.largecircle. B 1.97 2.48 2.74 .largecircle. 3.26 .largecircle.
3.84 .largecircle. 4.0- 7 .largecircle. D 2.10 2.58 3.32
.largecircle. 4.32 .largecircle. 5.35 .largecircle. 5.3- 0
.largecircle. E 2.10 2.81 .largecircle. 3.39 .largecircle. 4.61
.largecircle. 5.06 .lar- gecircle. 4.98 .largecircle. Edema A 0.00
0.23 0.23 .largecircle. 0.19 .largecircle. 0.16 0.12 B 0.00 0.23
.largecircle. 0.42 .largecircle. 0.10 0.13 0.00 D 0.06 0.19 0.55
.largecircle. 0.55 .largecircle. 0.35 .largecircle. 0.1- 2 E 0.00
0.29 .largecircle. 0.39 .largecircle. 0.39 .largecircle. 0.16 0.0-
3 Epithelialization A 0.00 0.90 .circle-solid. 2.32 .circle-solid.
3.48 .cir- cle-solid. 5.55 .circle-solid. 6.65 .circle-solid. B
0.00 0.71 .circle-solid. 2.06 .circle-solid. 3.58 .circle-solid.
5.84 .- circle-solid. 6.83 .circle-solid. D 0.00 0.68
.circle-solid. 2.06 .circle-solid. 2.68 .circle-solid. 5.61 .-
circle-solid. 6.33 .circle-solid. E 0.00 0.71 .circle-solid. 2.45
.circle-solid. 2.81 .circle-solid. 5.45 .- circle-solid. 6.68
.circle-solid. Maceration A 0.00 0.52 .largecircle. 1.45
.largecircle. 1.13 .largecircle.- 0.19 0.07 B 0.00 0.58
.largecircle. 1.61 .largecircle. 0.90 .largecircle. 0.16 0.0- 7 D
0.00 0.68 .largecircle. 1.90 .largecircle. 1.26 .largecircle. 0.26
.lar- gecircle. 0.43 E 0.00 0.45 .largecircle. 1.39 .largecircle.
1.65 .largecircle. 0.35 .lar- gecircle. 0.30 Scabbing A 0.00 0.00
0.13 0.94 .largecircle. 2.55 .largecircle. 1.32 .la- rgecircle. B
0.00 0.00 0.19 0.84 .largecircle. 1.97 .largecircle. 1.02
.largecircl- e. D 0.00 0.00 0.23 1.26 .largecircle. 1.45
.largecircle. 0.60 .largecircl- e. E 0.00 0.00 0.00 0.71
.largecircle. 1.97 .largecircle. 0.60 .largecircl- e.
.circle-solid. Indicates a statistically significant (p .ltoreq.
0.05) improvement compared to Baseline .largecircle. Indicates a
statistically significant (p .ltoreq. 0.05) worsening compared to
Baseline
Comparisons, based on the average change from the Baseline, were
made among the test sites using analysis of variance (ANOVA) with
pair-wise comparisons (Fisher's LSD). The rankings shown in Table 3
below are presented from the least to the greatest level of change,
which is presented in parentheses. Statistically significant
(p.ltoreq.0.05) differences between the test materials appear
below, and items marked by the same line are not significantly
different from one another.
TABLE-US-00003 TABLE 3 Comparisons Among Test Sites Based On The
Average Change From The Baseline ##STR00001##
Outcome of Human Study: Test Ointments A and B performed better
than Formulations D and E for erythema on Days 7, 14 and 21 Test
Ointments A and B performed better than Formulations D and E for
epithelialization on Day 7 Test Ointments A and B performed better
than Formulation E for maceration on Day 7 Test Formulation D
performed better than A for scabbing on Day 14 Test Formulations D
and E performed better than Ointment A for scabbing on Day 21
Overall, after one week of treatment, test Ointments A and B
performed better than D and E for erythema, epithelialization, and
maceration. With extended treatment, test Ointments A and B
continued to perform better for erythema.
Test Formulations D and E performed better than A and B for
scabbing, starting after two weeks of treatment. This result is due
to the highly occlusive nature of test Formulations D and E
(Petrolatum and Polysporin.TM., respectively) and therefore
suggests the application of the herbal formulation using semi and
full-occlusive devices such as bandages, dressings, etc, as
described herein.
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* * * * *
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